• The Korean Journal of Pain
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• 제23권1호
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• pp.1-10
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• 2010

Background: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. Methods: The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. Results: Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. Conclusions: The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.

• Journal of Radiation Protection and Research
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• 제32권1호
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• pp.1-8
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• 2007

도시지역의 방사능 오염으로 거주민의 피폭영향을 평가할 수 있는 모델 METRO-K를 개발하였다. 모델의 특성으로 1) 실험 또는 경험자료를 사용하기 때문에 수학식이 간단하여 이해가 쉬울 뿐 아니라 계산에 필요한 변수의 수가 적으며 2) 도시환경을 구성하는 5가지 기본표면 만을 사용하여 복잡하고 다양한 주변 환경을 쉽게 구성할 수 있으며 3) 각기 다른 오염 표면으로 인한 선량을 평가함으로써 표면마다 적합한 제염대책을 수립하는데 용이하다. 피폭자의 특정 위치에서 각기 다른 오염표면으로부터 받게 되는 선량은 감마에너지와 오염 표면별 공기커마 값을 데이터 라이브러리로 만들어 평가에 이용하였다. 유럽 도시지 역의 4가지 대표적 거주형태 에 대한 공기커마 값을 사용하여 우리나라 도시지역의 7가지 대표적 주거형태에 적합하도록 공기커마 값을 조합하여 적용하였다. 장기간 방사성물질의 누설을 고려하여 하루 단위의 핵종별 공기중 농도, 강우량, 핵종의 화학적 형태 구성분율이 입력되면 침적 후 시간에 따른 각기 다른 표면에서의 공기중 흡수선량률과 피폭자의 거주 위치에 따른 인체 선량률이 평가된다. 아파트 밀집지역에 대한 가상 오염 시나리오의 적용결과 피폭자의 거주위치 뿐 아니라 피폭자가 거주하는 주변 환경에 따라 인체 선량률은 확연한 차이를 나타냈다.

• 한국식품영양과학회지
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• 제45권6호
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• pp.903-910
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• 2016

엉겅퀴와 타임의 복합추출물인 MS-10이 여성호르몬 수용체를 가역적으로 활성화해 여성갱년기에 감소하는 에스트로겐이 효율적으로 사용될 수 있도록 작용한다는 것이 확인되었다. 12주간의 인체적용시험에서 MS-10은 안면홍조 및 야한증, 감각마비, 수면장애, 신경과민, 우울, 현기증, 피로, 관절 및 근육통, 두통, 가슴 두근거림(심계항진), 그리고 질건조 등의 여성갱년기 증상이 개선되었음이 확인되었다. 이러한 MS-10의 여성갱년기 증상 개선은 MS-10에 의한 insulin-like growth factor-1의 개선에 기인한 것으로 판단된다. MS-10은 여성갱년기 증상을 개선하는 천연소재 건강 기능식품으로 사용될 수 있다.

• 생명과학회지
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• 제23권5호
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• pp.650-656
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• 2013

내피세포 단백질 C 수용체(EPCR)가 트롬빈-트롬보모듈린 복합체에 의한 단백질 C (PC) 활성 증가에 중요한 역할을 한다. EPCR의 활성은 ecodomain의 분열과 수용성 단백질(sEPCR)로 분비함으로써 현저하게 변화한다. EPCR의 탈락은 tumor necrosis factor-${\alpha}$ converting enzyme (TACE)에 의해 매개된다. 토마토에서 발견된 라이코펜은 항산화 효과, 항암 효과, 항염증 효과를 가지고 있다. 그러나 EPCR 탈락에서의 라이코펜의 효과는 알려지지 않았다. 우리는 라이코펜이 PMA, TNF-${\alpha}$, IL-$1{\beta}$와 CLP에 의해 유도된 EPCR 탈락에 미치는 영향을 연구했다. 그 결과, 라이코펜은 TACE의 발현을 억제시켜 PMA, TNF-${\alpha}$, IL-$1{\beta}$와 CLP에 의해 매개된 EPCR 탈락을 저해함을 보여준다. 또한 라이코펜은 PMA가 유발한 p38, ERK1/2, JNK의 인산화를 감소시켰다. 이러한 결과를 토대로, 라이코펜은 EPCR 탈락의 저해를 통해 다양한 중증 혈관 염증 질병 치료를 위한 후보 물질이 될 수 있을 것이다.

• Genomics & Informatics
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• 제6권4호
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• pp.210-222
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• 2008

Due to the polygenic nature of cancer, it is believed that breast cancer is caused by the perturbation of multiple genes and their complex interactions, which contribute to the wide aspects of disease phenotypes. A systems biology approach for the identification of subnetworks of interconnected genes as functional modules is required to understand the complex nature of diseases such as breast cancer. In this study, we apply a 3-step strategy for the interpretation of microarray data, focusing on identifying significantly perturbed metabolic pathways rather than analyzing a large amount of overexpressed and underexpressed individual genes. The selected pathways are considered to be dysregulated functional modules that putatively contribute to the progression of disease. The subnetwork of protein-protein interactions for these dysregulated pathways are constructed for further detailed analysis. We evaluated the method by analyzing microarray datasets of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Using the strategy of microarray analysis, we selected several significantly perturbed pathways that are implicated in the regulation of progression of breast cancers, including the extracellular matrix-receptor interaction pathway and the focal adhesion pathway. Moreover, these selected pathways include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting interesting perturbed pathways that putatively play a role in the progression of breast cancer and provides an improved interpretability of networks of protein-protein interactions.

• BMB Reports
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• 제53권9호
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• pp.484-489
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• 2020

Epilepsy is a neurological disorder characterized by unpredictable seizures, which are bursts of electrical activity that temporarily affect the brain. Cereblon (CRBN), a DCAFs (DDB1 and CUL4-associated factors), is a well-established protein associated with human mental retardation. Being a substrate receptor of the cullin-RING E3 ubiquitin ligase (CRL) 4 complex, CRBN mediates ubiquitination of several substrates and conducts multiple biological processes. In the central nervous system, the large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel, which is the substrate of CRBN, is an important regulator of epilepsy. Despite the functional role and importance of CRBN in the brain, direct injection of pentylenetetrazole (PTZ) to induce seizures in CRBN knock-out mice has not been challenged. In this study, we investigated the effect of PTZ in CRBN knock-out mice. Here, we demonstrate that, compared with WT mice, CRBN knock-out mice do not show the intensification of seizures by PTZ induction. Moreover, electroencephalography recordings were also performed in the brains of both WT and CRBN knockout mice to identify the absence of significant differences in the pattern of seizure activities. Consistently, immunoblot analysis for validating the protein level of the CRL4 complex containing CRBN (CRL4^Crbn) in the mouse brain was carried out. Taken together, we found that the deficiency of CRBN does not affect PTZ-induced seizure.

• Archives of Pharmacal Research
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• 제28권9호
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• pp.995-1001
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• 2005

Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (I-L-receptors) and mouse vas deferens $(\delta-receptors)$ are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine $A_{2A}1\delta-opioid$ receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.

• 한국발생생물학회지:발생과생식
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• 제15권1호
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• pp.53-59
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• 2011

Sex steroid hormones are key molecules to prepare the decidual response and their levels are important in this process. Imbalances of the levels of steroid hormones are cause of implantation failure and other diseases including physical weakness. Androgen replacement therapy or selective androgen receptor modulator are used to overcome various diseases but long-term use may cause of side effects. In previous report, it is suggested that the steroid hormonal complexes derived from pig enhance the proliferation of satellite cell. Therefore, to evaluate the possible usage of steroid hormonal complex derived from pig testis (tS-C), the effects of tS-C on uterine response were studied using the model of artificial decidua. tS-C did not disturb the rhythmical estrus cycle. Artificial-induced decidual response was normally induced in tS-C administered mice. The histological characters of the decidua of tS-C administered mice were not different from the vehicle. The expression patterns of molecular markers of decidua were not different between vehicle and tS-C group. Collectively these results suggested that tS-C does not disturb the uterine responsibility to the embryo. In addition, our results suggested that tS-C can be applied to overcome the various problems such as loss of muscle mass and anemia.

• Molecules and Cells
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• 제23권3호
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• pp.363-369
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• 2007

Mitochondria play a central role in energy-generating processes and may be involved in the regulation of channels and receptors. Here we investigated TRPM7, an ion channel and functional kinase, and its regulation by mitochondria. Proton ionophores such as CCCP elicited a rapid decrease in outward TRPM7 whole-cell currents but a slight increase in inward currents with pipette solutions containing no MgATP. With pipette solutions containing 3 mM MgATP, however, CCCP increased both outward and inward TRPM7 currents. This effect was reproducible and fully reversible, and repeated application of CCCP yielded similar decreases in current amplitude. Oligomycin, an inhibitor of $F_1/F_O$-ATP synthase, inhibited outward whole-cell currents but did not affect inward currents. The respiratory chain complex I inhibitor, rotenone, and complex III inhibitor, antimycin A, were without effect as were kaempferol, an activator of the mitochondrial $Ca^{2+}$ uniporter, and ruthenium red, an inhibitor of the mitochondrial $Ca^{2+}$ uniporter. These results suggest that the inner membrane potential (as regulated by proton ionophores) and the $F_1/F_O$-ATP synthase of mitochondria are important in regulating TRPM7 channels.

• Journal of Plant Biotechnology
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• 제47권4호
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• pp.283-288
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• 2020

Although the evolution of Arabidopsis thaliana and humans diverged approximately 1.6 billion years ago, recent studies have demonstrated that protein function and cellular processes involved in disease response remain remarkably conserved. Particularly, γ-secretase, a multisubunit protein complex that participates in intramembrane proteolysis (RIP) regulation, is also known to mediate the cleavage of more than 80 substrates including the amyloid precursor protein (APP) and the Notch receptor. Although the genes (PS1/2, APH-1, PEN-2, and NCT) coding for the γ-secretase complex components are present in plant genomes, their function remains largely uncharacterized. Given that the deposition of 42 amino acid long amyloid-β peptides (hAβ₄₂) is thought to be one of the main causes of Alzheimer's disease, we aimed to examine the physiological effects of hAβ₄₂ peptides on plants. Interestingly, we found that Arabidopsis protoplast death increased after 24 h of exposure to 3 or 5 µM hAβ₄₂ peptides. Furthermore, transgenic Arabidopsis plants overexpressing the hAβ₄₂ gene exhibited changes in primary root length and silique phyllotaxy. Taken together, our results demonstrate that hAβ₄₂ peptides, a metazoan protein, significantly affect Arabidopsis protoplast viability and plant morphology.